Tratamiento anticoagulante oral: una historia interminable / Oral anticoagulant treatment: a non ending history

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Fixed-dose low-molecular-weight heparin for secondary prevention of venous thromboembolism in patients with disseminated cancer: a prospective cohort study.

INTRODUCTION: Secondary prevention of venous thromboembolism (VTE) with vitamin K antagonists is often problematic in patients with cancer. We prospectively evaluated the effectiveness and safety of long-term subcutaneous dalteparin in a series of consecutive patients with symptomatic VTE and metastatic cancer. PATIENTS AND METHODS: The study included 203 patients, aged 36-96 years. The initial treatment consisted of a 7-day course of subcutaneous dalteparin according to body weight. Then, patients received a fixed dose of 10 000 IU dalteparin once daily for at least 3 months. In patients developing transient thrombocytopenia the dose was reduced to 5000 IU daily while the platelet count remained <50,000; and to 2500 IU daily while it remained <10 000. Patients undergoing any surgical intervention during the study were put on 5000 IU daily during the first 4 days, switching thereafter to 10,000 IU. Patients undergoing any other invasive procedure (i.e. biopsies, punctures) received a 5000 IU dose the same day, instead of 10 000 IU. RESULTS: Eleven patients (5.4%) developed major bleeding complications (6 fatal) during the 3-month study period, and 18 patients (8.9%) developed VTE recurrences (2 patients died). There were no higher complication rates in patients with either liver or brain metastases, nor during thrombocytopenia, surgery or invasive procedures. CONCLUSIONS: Fixed dose 10,000 IU subcutaneous dalteparin once daily for 3 months was not associated with more complications in patients with liver or brain metastases. The dose adjustment for patients with thrombocytopenia, surgery or invasive procedures was safe too.

Platelet count and the risk of bleeding in hospitalized patients with venous thromboembolism starting anticoagulant therapy.

In a series of patients with pulmonary embolism (PE) we have previously demonstrated that the risk of recurrent PE was inversely correlated to platelet count (PlC) levels. To find out whether PlC levels were also associated to a different incidence of heparin-related bleeding complications, we report our experience with 1,103 consecutive patients with venous thromboembolism (VTE) receiving full-dose heparin therapy. Six points of clinical and laboratory information were recorded on admission and then compared to the development of bleeding: the patient's age and sex; the etiology of VTE; the type of heparin used (unfractioned, UFH, vs. low-molecular-weight, LMWH), the presence or lack of PE findings on lung scan, and the PC levels on admission. Bleeding occurred in 64/1,103 patients (6%). Patients who bled were significantly older than those who did not (72 +/- 11 vs. 64 +/- 17 years; p = 0.0005). There were no significant differences in bleeding rate according to any of the risk factors that could have predisposed to VTE, but patients treated with UFH bled significantly more frequently than those on LMWH (48/636 vs. 16/467; odds ratio: 2.30; 95% confidence interval: 1.25-4.28). Finally, mean PlC levels were significantly lower at VTE diagnosis in patients who subsequently bled (227 +/- 112 vs. 262 +/- 110 x 10(9) liters-1; p = 0.01). The logistic regression analysis confirmed that all three variables were independent risk factors for bleeding complications. This is the first study to demonstrate that PlC levels (within the normal range) are inversely correlated with the risk of heparin-related bleeding. These findings may be interest not only from the point of view of pathogenesis but also clinically, as they may be used in the decision as to which VTE patients could receive heparin therapy at home.

Analysis of compliance with oral contraception in Spain.

OBJECTIVE: The study was designed to analyze factors related to compliance in oral hormonal contraception in Spain. METHOD: A review study and a multicenter analysis of experience of compliance by 300 doctors, by means of a questionnaire and discussion about the determinants of contraceptive use. RESULTS: Compliance is a major problem in Spain, being influenced mainly by side-effects, the general perception of the method and personal factors. The different factors involved in non-compliance in Spain were analyzed, with regard to the perspective of the professionals. CONCLUSIONS: Strategies to improve compliance in Spain aim mainly at improving the general perception of the method and the accessibility of family planning centers. Factors associated with compliance are still not well known in our country. Better knowledge of the determinants of non-compliance in Spain is needed. For this purpose, another research group was formed to conduct a national study among women.

Preoperative platelet count and postoperative blood loss in patients undergoing hip surgery: an inverse correlation.

In a previous study we tried to assess the clinical usefulness of platelet count (PlC) to confirm whether postoperative pulmonary embolism could be suspected early. Unexpectedly, the 19 patients who subsequently developed pulmonary embolism had significantly lower mean PlC levels even before surgery. In an attempt to discover whether the preoperative PlC levels were associated with a different incidence of postoperative blood loss, we decided to retrospectively study the relationship between preoperative PlC levels and the consequences of blood loss. There were 459 consecutive patients undergoing hip surgery. After excluding 5 patients who died during the first 3 postoperative days, and 16 patients who bled from a definitive anatomic site, there were 438 patients. Blood loss was considered to be excessive when two or more of the following conditions were present: (1) total transfusion requirements exceeding 1,000 ml whole blood or 2 units of packed red cells; (2) a drop in hemoglobin level of 5 g/dl or more, and (3) a hemoglobin level below 8 g/dl at any moment during the first 8 postoperative days. Blood loss was considered to be excessive in 91 patients. Preoperative PlC levels were significantly lower in these patients as compared to patients without the condition (204 +/- 52 vs. 236 +/- 79 x 10(9) liter-1; p = 0.0002). When patients were classified according to the quartiles of preoperative PlC, the odds ratio of developing excessive blood loss was 0.69 (95% CI: 0.38-1.26) in patients in the second quartile; 0.57 (95% CI: 0.30-1.06) in the third quartile, and 0.27 (95% CI: 0.13-0.57) in patients in the highest quartile. After adjusting for age, sex, type of surgery and type of prophylaxis, the preoperative PlC levels maintained a statistically significant inverse correlation with postoperative blood loss.

Effects of long-term therapy with either heparin or low-molecular-weight heparin on serum lipid levels. A prospective study.

Beside the anticoagulant and antithrombotic activity, heparin also exerts a lipolytic activity. In a prospective study on patients with venous thromboembolism and some contraindications to coumarin therapy, a low-molecular-weight heparin (Fragmin) was compared to unfractioned (UF) heparin in terms of both efficacy and safety. A secondary aim was to study the influence of both types of heparin on serum lipid levels. Sixty-six consecutive patients who were not taking concomitant treatment with lipid-lowering drugs entered the study. Patients received treatment with either UF heparin, 10,000 IU s.c., b.d., or Fragmin 5,000 IU anti-factor Xa s.c., b.d. for a period of 3 or 6 months, according to whether the initial diagnosis was deep venous thrombosis or pulmonary embolism. Each patient was followed up at 6-weekly intervals, and blood samples were obtained at discharge, and then 6 and 12 weeks after discharge. Finally, a further sample was obtained 3 months after therapy was discontinued. Total cholesterol levels increased significantly in both groups of patients: levels increased from 193 +/- 56 to 246 +/- 63 mg/dl in the UF heparin group (p < 0.001), and from 189 +/- 53 to 222 +/- 47 mg/dl in the Fragmin group (p < 0.05). The increase was mostly due to a very strong increase in HDL cholesterol levels in patients receiving UF heparin (from 46 +/- 12 to 71 +/- 23 mg/dl; p < 0.000005). Three months after discharge, HDL cholesterol levels were significantly higher in patients taking UF heparin than in patients in Fragmin (p = 0.006). By contrast, patients on Fragmin exhibited a significant increase in LDL cholesterol levels: from 112 +/- 39 to 139 +/- 37 mg/dl; p < 0.01.

Effects of recombinant hirudin on D dimer levels before and after experimental venous thrombosis.

In a randomized, blind study, the effect of saline, a low-molecular-weight heparin (Fragmin), and a recombinant hirudin (CGP 39393) on thrombin-antithrombin (TAT) complexes and D dimer (DD) levels were studied in 60 rabbits. The drugs were always injected subcutaneously 2 h before the induction of thrombosis in the jugular vein by a combination of endothelial damage and flow reduction. A sample of blood was obtained just before surgery, and a further sample was obtained 10 min after thrombus formation. No significant differences were found in TAT plasma levels between the different study agents, either before or after thrombus development. However, 2 h after drug administration DD values were significantly lower in hirudin-treated animals (292 +/- 69 vs. 372 +/- 138 ng/ml; p < 0.05). Then, after thrombus formation, DD levels significantly increased in all three groups of animals, as compared to baseline levels. But the increase was significantly higher in hirudin-treated rabbits; DD levels after thrombus development were significantly higher in this group as compared to placebo (779 +/- 188 vs. 664 +/- 152 ng/ml; p < 0.05). There are no previous reports in the literature about the effect of hirudin on DD levels. Our hypothesis is that the effect of hirudin on DD may be the result of its ability to inhibit the thrombin-induced thrombus growth. If the thrombus is not allowed to grow then it will lyse more quickly, producing more DD and the process will not be impaired by the constant deposition of fibrin.(ABSTRACT TRUNCATED AT 250 WORDS)

[Acute basophilic leukemia with an intense erythroblastic reaction]. / Leucemia aguda a basófilos con intensa reacción eritroblástica.

A patient is presented who had acute basophilic leukaemia with intense erythroblastic reaction. The patient, a 66 year-old man, complained of general malaise, increased abdominal perimeter and melena. Leucocytosis, as well as severe anaemia and thrombocytopenia, were found in his peripheral blood. Basophils were present in all maturation stages, along with 7% blast-cells showing basophilic stippling, and there were 210 erythroblasts per 100 white cells. Erythropoietic hyperplasia (75%) was found in the bone-marrow aspirate, without dyserythropoietic signs; the PAS-stain reaction was negative. Of the non-erythroid cells, 63% were basophils and 34% blast-cells, some of them showing basophilic stippling plus metachromasia for tholuidin-blue, positivity for omegaexonuclease and negativity for peroxidase stains. The diagnosis of acute basophilic leukaemia was confirmed upon demonstration of basophilic stippling in the ultrastructural study of the blast-cells. The patient developed acute liver failure and renal insufficiency which led him to death. The basis of the diagnosis of acute basophilic leukaemia is discussed, as well as the differential diagnosis with other conditions presenting with basophilia and the probably reactive erythroblastic increase appearing in this case.

Effects of inhaled platelet activating factor on bronchial responsiveness in patients with symptomatic and asymptomatic pulmonary embolism.

To determine the possible role of platelet-activating factor (PAF) in pulmonary embolism (PE), the reactivity of the airways to inhaled PAF, using doses ranging from 6.25 to 400 micrograms, was examined in 24 patients with a past episode of PE. Twelve of these patients had experienced acute respiratory insufficiency during the episode (with or without additional symptoms). None of the remaining 12 patients had experienced any respiratory symptoms during the PE episode. Diagnosis was established by means of a ventilation-perfusion lung scan performed when admitted to the hospital because of deep venous thrombosis (DVT) in the lower limbs. Nonspecific bronchial reactivity as measured by the response to bronchoprovocation testing with methacholine showed no significant differences between both groups. PAF caused a dose-dependent bronchoconstriction defined by at least a 35 percent decrease in specific airway conductance (SGaw) in all patients. The average dose of PAF needed to decrease SGaw 35 percent was significantly lower in patients who had had a symptomatic PE than in those with asymptomatic PE (p = 0.011). This finding suggests that patients who suffered from symptomatic PE may present a greater airway reactivity to inhaled PAF. This different behavior might explain the existence of some of the respiratory symptoms of PE, which could be attributed to PAF-related effects. However, additional studies are needed to evaluate the role of PAF in PE.

[Heparin-induced hemorrhage in the treatment of venous thromboembolism]. / Hemorragias por heparina en el tratamiento del tromboembolismo venoso.

Retrospective study about the frequency of hemorrhagic complications (258 patients) in the treatment of venous thrombosis and/o pulmonary embolism, with heparin. Heparin was intermittently administered by endovenous way and controlled during the ten first days. Mostly of the big hemorrhages happened between the seventh and the tenth day, in digestive and urinary system mainly.

Adverse effects of three different forms of heparin therapy: thrombocytopenia, increased transaminases, and hyperkalaemia.

A prospective study has been made of the incidence of changes in transaminase levels, hyperkalaemia and thrombocytopenia in three groups of patients: 89 consecutive patients with venous thrombosis receiving therapeutic heparinization, 49 patients admitted because of hip fracture and receiving prophylactic low-dose conventional heparin, and 43 patients admitted because of hip fracture and randomly allocated to receive low molecular weight heparin. Laboratory measurements were made on admission and 8 days after commencing heparin. Only two patients on high-dose heparin developed thrombocytopenia. Increased transaminases were frequent with conventional heparin (18% and 32% of patients on high-dose heparin developed abnormal AsT and AlT values, respectively compared with 14% and 17% patients on low dose therapy). In contrast, only one patient on low molecular weight heparin developed abnormal AlT activity. Hyperkalaemia was uncommon in patients on any form of heparin therapy, and severe hyperkalaemia occurred in only one patient.